This is a study to determine the safety of multiple doses of CDX-0159 in patients with Chronic Spontaneous Urticaria.

The purpose of the study is to explore the safety, pharmacodynamics, and pharmacokinetics of ascending doses of CDX-0159 in patients with Chronic Spontaneous Urticaria who remain symptomatic despite treatment with antihistamines.

There is a screening period of up to 2 weeks, a 12-week double-blind treatment period and a 12-week follow-up period after treatment. Patients will receive multiple doses of CDX-0159 or placebo as add on therapy to their antihistamine.

Key Inclusion Criteria:

1. Males and females, 18 - 75 years old.

2. Diagnosis of chronic spontaneous urticaria (CSU) despite the use of H1-antihistamines alone or in combination with H2-antihistamines and/or leukotriene receptor antagonists, as defined by:

   1. Diagnosis of CSU for >/= 6 months.
   2. The presence of itch and hives for >/= 6 consecutive weeks at any time prior to Visit 1 despite current use of H1-antihistamines.
   3. UAS7 of >/= 16 and HSS7 of >/= 8 during the 7 days before treatment
   4. In-clinic UAS >/= 4 on one of the screening visit days
   5. Use of H1-antihistamines alone or in combination with H2-antihistamines and/or leukotriene receptor antagonists for at least 3 days immediately prior to study entry and throughout the study.

3. Other than CSU, have no other significant medical conditions that would cause additional risk or interfere with study procedures.

4. Normal blood counts and liver function tests.

5. Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for 150 days afterwards after treatment.

6. Willing and able to complete a daily symptom electronic diary for the duration of the study and adhere to the study visit schedule.

Key Exclusion Criteria:

1. Women who are pregnant or nursing.
2. Cleary defined cause for chronic urticaria.
3. Known HIV, hepatitis B or hepatitis C infection.
4. Vaccination with a live vaccine within 4 weeks prior to study drug administration (subjects must agree to avoid vaccination during the study). Inactivated vaccines are allowed such as seasonal influenza for injection.
5. History of anaphylaxis.

There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.